Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer
Abstract Objectives We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD). Materials and Methods From EGC patients who underwent ESD, bulk RNA sequencing was performed on non...
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| Format: | Article |
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Wiley
2024-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70104 |
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| author | Bokyung Kim Harim Chun Jongwon Lee Miree Park Yoonjin Kwak Jung Mogg Kim Sang Gyun Kim Ji Kon Ryu Jungmin Choi Soo‐Jeong Cho |
| author_facet | Bokyung Kim Harim Chun Jongwon Lee Miree Park Yoonjin Kwak Jung Mogg Kim Sang Gyun Kim Ji Kon Ryu Jungmin Choi Soo‐Jeong Cho |
| author_sort | Bokyung Kim |
| collection | DOAJ |
| description | Abstract Objectives We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD). Materials and Methods From EGC patients who underwent ESD, bulk RNA sequencing was performed on non‐cancerous gastric mucosa samples at the time of initial EGC diagnosis. This included 23 patients who developed MGC, and 23 control patients without additional gastric neoplasms for over 3 years (1:1 matched by age, sex, and Helicobacter pylori infection state). Candidate differentially‐expressed genes were identified, from which biomarkers were selected using real‐time quantitative polymerase chain reaction and cell viability assays using gastric cell lines. An independent validation cohort of 55 MGC patients and 125 controls was used for marker validation. We also examined the severity of gastric intestinal metaplasia, a known premalignant condition, at initial diagnosis. Results From the discovery cohort, 86 candidate genes were identified of which KDF1 and CDK1 were selected as markers for MGC, which were confirmed in the validation cohort. CERB5 and AKT2 isoform were identified as markers related to intestinal metaplasia and were also highly expressed in MGC patients compared to controls (p < 0.01). Combining these markers with clinical data (age, sex, H. pylori and severity of intestinal metaplasia) yielded an area under the curve (AUC) of 0.91 (95% CI, 0.85‐0.97) for MGC prediction. Conclusion Assessing biomarkers in non‐cancerous gastric mucosa may be a useful method for predicting MGC in EGC patients and identifying patients with a higher risk of developing MGC, who can benefit from rigorous surveillance. |
| format | Article |
| id | doaj-art-b9437255a4394ecebbeeb05b48179e4d |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-b9437255a4394ecebbeeb05b48179e4d2025-08-20T02:48:12ZengWileyCancer Medicine2045-76342024-08-011316n/an/a10.1002/cam4.70104Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancerBokyung Kim0Harim Chun1Jongwon Lee2Miree Park3Yoonjin Kwak4Jung Mogg Kim5Sang Gyun Kim6Ji Kon Ryu7Jungmin Choi8Soo‐Jeong Cho9Department of Internal Medicine and Liver Research Institute Seoul National University Hospital, Seoul National University College of Medicine Seoul KoreaDepartment of Biomedical Sciences Korea University College of Medicine Seoul KoreaDepartment of Biomedical Sciences Korea University College of Medicine Seoul KoreaDepartment of Internal Medicine and Liver Research Institute Seoul National University Hospital, Seoul National University College of Medicine Seoul KoreaDepartment of Pathology Seoul National University Hospital Seoul KoreaDepartment of Microbiology Hanyang University College of Medicine Seoul KoreaDepartment of Internal Medicine and Liver Research Institute Seoul National University Hospital, Seoul National University College of Medicine Seoul KoreaDepartment of Internal Medicine and Liver Research Institute Seoul National University Hospital, Seoul National University College of Medicine Seoul KoreaDepartment of Biomedical Sciences Korea University College of Medicine Seoul KoreaDepartment of Internal Medicine and Liver Research Institute Seoul National University Hospital, Seoul National University College of Medicine Seoul KoreaAbstract Objectives We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD). Materials and Methods From EGC patients who underwent ESD, bulk RNA sequencing was performed on non‐cancerous gastric mucosa samples at the time of initial EGC diagnosis. This included 23 patients who developed MGC, and 23 control patients without additional gastric neoplasms for over 3 years (1:1 matched by age, sex, and Helicobacter pylori infection state). Candidate differentially‐expressed genes were identified, from which biomarkers were selected using real‐time quantitative polymerase chain reaction and cell viability assays using gastric cell lines. An independent validation cohort of 55 MGC patients and 125 controls was used for marker validation. We also examined the severity of gastric intestinal metaplasia, a known premalignant condition, at initial diagnosis. Results From the discovery cohort, 86 candidate genes were identified of which KDF1 and CDK1 were selected as markers for MGC, which were confirmed in the validation cohort. CERB5 and AKT2 isoform were identified as markers related to intestinal metaplasia and were also highly expressed in MGC patients compared to controls (p < 0.01). Combining these markers with clinical data (age, sex, H. pylori and severity of intestinal metaplasia) yielded an area under the curve (AUC) of 0.91 (95% CI, 0.85‐0.97) for MGC prediction. Conclusion Assessing biomarkers in non‐cancerous gastric mucosa may be a useful method for predicting MGC in EGC patients and identifying patients with a higher risk of developing MGC, who can benefit from rigorous surveillance.https://doi.org/10.1002/cam4.70104biomarkersendoscopic resectiongastric cancerRNA sequencingwhole exome sequencing |
| spellingShingle | Bokyung Kim Harim Chun Jongwon Lee Miree Park Yoonjin Kwak Jung Mogg Kim Sang Gyun Kim Ji Kon Ryu Jungmin Choi Soo‐Jeong Cho Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer Cancer Medicine biomarkers endoscopic resection gastric cancer RNA sequencing whole exome sequencing |
| title | Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer |
| title_full | Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer |
| title_fullStr | Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer |
| title_full_unstemmed | Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer |
| title_short | Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer |
| title_sort | predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer |
| topic | biomarkers endoscopic resection gastric cancer RNA sequencing whole exome sequencing |
| url | https://doi.org/10.1002/cam4.70104 |
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